KRE5 Suppression Induces Cell Wall Stress and Alternative ER Stress Response Required for Maintaining Cell Wall Integrity in Candida glabrata.

KRE5 Suppression Induces Cell Wall Stress and Alternative ER Stress Response Required for Maintaining Cell Wall Integrity in Candida glabrata.
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KRE5抑制诱导细胞壁应力和维持念珠菌中细胞壁完整性所需的替代性ER应力反应。

DOI:
10.1371/journal.pone.0161371
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Shibata N
Shibata N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tanaka Y;Sasaki M;Ito F;Aoyama T;Sato-Okamoto M;Takahashi-Nakaguchi A;Chibana H;Shibata N

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真菌细胞壁完整性的维持是细胞正常生长、分裂、菌丝形成和抗真菌耐受性所必需的。我们观察到内质网应激调节光滑念珠菌细胞壁的完整性,光滑念珠菌具有独特的未折叠蛋白反应机制的进化机制。四环素介导的KRE 5(编码位于内质网中的预测UDP-葡萄糖:糖蛋白葡萄糖基转移酶)抑制显著增加细胞壁几丁质含量并降低细胞壁β-1,6-葡聚糖含量。KRE 5阻遏通过细胞壁完整性信号通路诱导内质网应激相关基因表达和MAP激酶通路激活,包括Slt 2 p和Hog 1 p磷酸化。此外,钙调神经磷酸酶途径负调节细胞壁完整性,但不减少β-1,6-葡聚糖含量。这些结果表明,KRE 5是维持内质网稳态和细胞壁完整性所必需的,并且钙调神经磷酸酶途径作为细胞壁中几丁质-葡聚糖平衡的调节剂和作为C.光滑的
The maintenance of cell wall integrity in fungi is required for normal cell growth, division, hyphae formation, and antifungal tolerance. We observed that endoplasmic reticulum stress regulated cell wall integrity in Candida glabrata, which possesses uniquely evolved mechanisms for unfolded protein response mechanisms. Tetracycline-mediated suppression of KRE5, which encodes a predicted UDP-glucose:glycoprotein glucosyltransferase localized in the endoplasmic reticulum, significantly increased cell wall chitin content and decreased cell wall β-1,6-glucan content. KRE5 repression induced endoplasmic reticulum stress-related gene expression and MAP kinase pathway activation, including Slt2p and Hog1p phosphorylation, through the cell wall integrity signaling pathway. Moreover, the calcineurin pathway negatively regulated cell wall integrity, but not the reduction of β-1,6-glucan content. These results indicate that KRE5 is required for maintaining both endoplasmic reticulum homeostasis and cell wall integrity, and that the calcineurin pathway acts as a regulator of chitin-glucan balance in the cell wall and as an alternative mediator of endoplasmic reticulum stress in C. glabrata.